It has been known for several years that the muscle cells of the atrial myocardium in mammals contain, in addition to contractile elements similar to those found in ventricular fibers, a highly developed Golgi complex, a relatively high proportion of rough endoplasmic reticulum, and numerous membrane-bound storage granules, referred to as specific atrial granules. No such granules appear to exist in ventricular muscle cells. Peptide isolates from the atrial granules have been shown to exhibit potent diuretic, natriuretic and vasodilatory properties. In my earlier application Ser. No. 473,442, a peptide defined by 28 amino acid residues was described and in my application Ser. No. 546,817 that peptide was defined as a 28 residue disulfide-looped structure and named Cardionatrin I. In commonly assigned application Ser. No. 626,219 filed June 29, 1984 by Peter L. Davies the sequence of a cloned cDNA for rat cardionatrin precursor has been established. The precursor, preprocardionatrin, has been shown to contain 152 amino acids and cardionatrin I containing a 28 amino acid sequence beginning at residue 123 thereof may be cleaved therefrom.
Others have verified the preprocardionatrin sequence and have reported a multitude of different peptides which differ from Cardionatrin I by a few amino acids more or less. In contrast, I have consistently observed only three other bio-active peptides, cardionatrins II, III and IV (as hereinafter defined) which have significantly larger molecular weights than Cardionatrin I, and which can be derived from a common precursor.